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A polyene cyclization converts a chain containing several carbon–carbon double bonds into one or more rings. A suitable initiating event can generate a reactive centre that attacks a later double bond, producing another reactive centre and allowing a cascade of ring closures.

The folded chain's geometry helps determine which rings and stereogenic centres form. In biosynthesis, enzyme-controlled cyclization of precursors related to squalene constructs complex steroid frameworks. The double bonds need not all belong to one continuous conjugated system. A plausible drawn cascade also needs compatible reaction kinetics and a three-dimensional conformation; connectivity alone does not guarantee that a proposed sequence occurs.

Squalene is a thirty-carbon unsaturated hydrocarbon, ${\mathrm{C}}_{30}{\mathrm{H}}_{50}$, with six carbon–carbon double bonds.^[ref] Its long chain can be folded and cyclized during the biosynthesis of sterols, making it a useful connection between an acyclic precursor and complex fused-ring structures.

The sequence and geometry of the double bonds matter: they determine which groups can approach during a cyclization. Biological pathways use enzymes to control that geometry and the reaction cascade. Hydrogenation of the double bonds changes the compound's identity, rather than merely purifying the original squalene.

Squalene epoxidase is a flavin-dependent enzyme that converts squalene to 2,3-epoxysqualene during sterol synthesis. The reaction introduces an oxygen-containing epoxide group before later cyclization steps construct the sterol ring system. In the human enzyme, FAD supports oxidation using molecular oxygen and reducing equivalents supplied through a reductase. ^[ref]

This step illustrates that biosynthetic pathways control both carbon skeletons and oxidation state. Adding a double-bond oxygen functionality and subsequently forming rings are different chemical operations performed by different enzymes. An assay of pathway output cannot locate an inhibition point without measurements of intermediates or a direct enzyme assay.

William S. Johnson developed a stereoselective orthoester variant of the Claisen rearrangement. The 1970 report connects the method with formation of trans-trisubstituted carbon–carbon double bonds and the synthesis of squalene.^[ref]